The goal of this research proposal is to study the control mechanisms that regulate immunoglobulin (Ig) or antibody synthesis. In this proposal, five independent but closely related experiments are planned. The first two experiments are designed to elaborate the complex nature of the Ig heavy chain variable region (VH) sub-subgroups. By using the "homogenous" antibodies as immunoadsorbents and by using the possible sequential suppression release of the sub-subgroups, I will obtain Ig populations that are unique for the sub-subgroups. Once these Ig populations are obtained, a more detailed analysis of the complex VH region genes will be possible. In the third experiment, I propose to induce auto-anti-allotype antibody in homozygous suppressed rabbits. The potential significance of these experiments is great, since it may provide experimental evidence supporting the network theory of the immune system, may provide an experimental model for the study the autoimmunity, may lead to development of gamma-globulinemic rabbits, and may yield information on the presence of latent allotypes. Furthermore, the outcome of this experiment may provide a systematic way to produce homozygous suppressed rabbits, thus making available a supply of the VHa negative Ig molecules. In a fourth experiment, the gene expression of two allotypic loci (a VHa and a C micron n gene) in trans chromosomal positions will be suppressed simultaneously. By this manipulation, enhancement of possible latent allotypes and VH - CH recombinant molecules may occur. The fifth experiment is designed to induce specifically two "homogeneous" antibodies bearing cross-reactive idiotypes as has been observed by Kindt et al., (1973). This aim will be accomplished by taking advantage of allotype expression of the anti-Ars-anti-body. The outcome of this experiment may provide additional evidence supporting the episomal insertion hypothesis.